PB2343: TRIAL IN PROGRESS: PHASE 3 TRIAL EVALUATING THE EFFICACY AND SAFETY OF ODRONEXTAMAB VERSUS STANDARD OF CARE THERAPY IN RELAPSED/REFRACTORY AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA (OLYMPIA-4)
Authors: Eliza A. Hawkes, Tae Min Kim, Manjusha Namuduri, Ashish Risal, Biyi Shen, Dina Flink, Min Zhu, Siobhán Nolan, Jurriaan Brouwer-Visser, Aafia Chaudhry, Srikanth Ambati, Hesham Mohamed, Seok-Goo Cho
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Aggressive B-cell non-Hodgkin lymphomas (B-NHLs) follow a rapidly progressive clinical course and lead to frequent constitutional symptoms. First-line treatment for aggressive B-NHLs typically comprises chemotherapy plus an anti-CD20 antibody (Ab), with ~50% of patients (pts) cured by this treatment. For those pts who are relapsed/refractory (R/R) to first-line therapy, autologous stem cell transplant (ASCT) remains the only potentially curative strategy, although not all pts tolerate salvage/high-dose chemoimmunotherapy leading to ASCT and a notable proportion of pts will relapse post-transplant. Alternative second-line options include CAR T therapies, although efficacy data have been inconsistent between treatments, and CAR T treatments may not be feasible for many pts. With both CAR T treatments and ASCT limited by accessibility, there is an urgent need for novel, off-the-shelf, therapies. Odronextamab is a CD20×CD3 bispecific antibody that triggers T-cell-mediated cytotoxicity of malignant B cells. In clinical trials, odronextamab achieved clinically meaningful responses in pts with heavily pretreated, R/R DLBCL, including in those pts with prior CAR T treatment (Bannerji, et al. Lancet Haematol, 2022; Kim, et al. ASH, 2022). In addition, odronextamab showed a generally manageable safety profile with an optimized step-up regimen (0.7/4/20 mg), with minimal severe grade cytokine release syndrome that occurred mainly with Cycle 1 step-up. These data support further assessment of odronextamab across subtypes of aggressive R/R B-NHL. Aims: To evaluate the efficacy and safety of odronextamab monotherapy versus current standard of care (SOC) treatment in pts with aggressive R/R B-NHL. Methods: OLYMPIA-4 is a Phase 3, randomized, open-label, study that will take place at ~200 sites globally. Up to 216 pts will be randomized (1:1) to fixed duration treatment with IV odronextamab (1 year) or SOC, with randomization stratified by timing of relapse to first-line therapy and by pt score on the secondary age-adjusted International Prognostic Index. Odronextamab induction treatment will be given for 4×21-day cycles, with step-up dosing during Cycle (C) 1 (Figure). Pts will receive the full dose of odronextamab from C2 to 4, followed by odronextamab maintenance treatment until 1 year from start of treatment, progressive disease, or death (whichever is sooner). SOC will comprise salvage therapy (ICE±R, DHAP±R, or GDP±R) for up to 3×21-day cycles, followed by ASCT. Pts with no optimal response to salvage therapy or ASCT may cross over to receive odronextamab for 1 year. Eligible pts are ≥18 years of age with aggressive B-NHL, that is primary refractory or has relapsed ≤1 year from the start of first-line therapy, and intend to proceed to ASCT. Other key eligibility criteria include measurable disease, ECOG PS ≤1, and adequate organ function status. Exclusion criteria include primary CNS lymphoma, significant CNS pathology, and evidence of any active infection. All pts will provide informed consent. Results: The primary endpoint is event-free survival (time to disease progression, start of new anti-lymphoma therapy, or death), assessed by independent central review. Key secondary endpoints are progression-free survival, best overall response, and changes in physical functioning by the EORTC QLQ-C30. Summary/Conclusion: OLYMPIA-4 will determine the utility of odronextamab monotherapy as a novel alternative treatment option for pts with aggressive R/R B-NHL who have relapsed early (within 1 year) and/or were refractory to first-line therapy.Keywords: Relapsed lymphoma, Diffuse large B cell lymphoma, Bispecific, Non-Hodgkin’s lymphoma